Co esponding au ho : Jude E. Okokon
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
Tel ai ia occiden alis seed ex ac and ac ions mi iga ed doxo ubicin-induced
ca dio oxici y in a s
Ugochi Q. Nwosu 1, Kenne h Chidi Opa a 2, Chinyelu C. Osigwe 3, Ugonma F. Uwaeme 3, Unyime A. Fabian 4 and
Jude E. Okokon 1, *
1 Depa men o Pha macology and Toxicology, Facul y o Pha macy, Uni e si y o Uyo, Uyo, Nige ia.
2 Depa men o Family Medicine, Fede al Teaching Hospi al, Owe i, Imo S a e, Nige ia.
3 Depa men o Pha macology and Toxicology, Facul y o Pha macy, Madonna Uni e si y Nige ia, Elele campus, Ri e s
S a e, Nige ia.
4 Facul y o Allied Heal h sciences, Depa men o Medical Labo a o y Sciences Uni e si y o Uyo, Uyo, Nige ia.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
Publica ion his o y: Recei ed on 21 Augus 2025; e ised on 01 Oc obe 2025; accep ed on 03 Oc obe 2025
A icle DOI: h ps://doi.o g/10.30574/gscbps.2025.33.1.0375
Abs ac
Tel ai a occiden alis Hook (Cucu bi aceae) seeds a e used in he p epa a ion o soups and as medicine adi ionally o
ea a ious diseases. This s udy was designed o in es iga e he an ido al po en ials o he c ude ex ac and ac ions
o Tel ai ia occiden alis seed agains doxo ubicin-induced hea oxici y in a s. The seed ex ac (138-553 mg/kg) and
ac ions (dichlo ome hane and aqueous, 276 mg/kg) o he plan we e in es iga ed o an ioxida i e s ess and
ca diop o ec i e po en ials agains doxo ubicin-induced hea oxici y in a . E ec o he seed ex ac and ac ions on
ca diac ma ke enzymes, oxida i e s ess ma ke s, lipid p o ile indices and hea his ology we e used as pa ame e s o
assess he ca diop o ec i e e ec o he ex ac and ac ions. The seed ex ac and ac ions (138-553 mg/kg)
signi ican ly (p<0.05-0.01) educed he se um le els o CK-MB, LDH and oponin I ha we e ele a ed by doxo ubincin.
Also, he le els o GSH, SOD, GPx and CAT in he hea ha we e dec eased by doxo ubicin we e signi ican ly (p<0.01)
ele a ed and he aised MDA le el was educed by he seed ex ac and ac ions. The seed ex ac and ac ions also
educed signi ican ly (p<0.05) he se um le els o o al choles e ol, iglyce ides, LDL and VLDL o he ea ed a s
ele a ed by doxo ubicin. His ology sec ions o hea s o ex ac / ac ions - ea ed animals showed educ ions in he
pa hological ea u es compa ed o he o gano oxic- ea ed animals. The chemical pa hological changes we e consis en
wi h his opa hological obse a ions sugges ing ma ked ca diop o ec i e po en ials. The an i- oxic e ec o his plan
may in pa be media ed h ough he chemical cons i uen s o he plan . The seed ex ac o Tel ai ia occiden alis
possesses an i- oxican p ope ies which can be exploi ed in he ea men o poisoning.
Keywo ds: Tel ai ia occiden alis; An i-Toxican ; Oxida i e S ess; Ca diop o ec i e; An ioxidan
1. In oduc ion
D ug-induced ca dio oxici y is a se ious clinical challenge which is associa ed wi h so many clinically use ul d ugs
especially cy o oxic d ugs one o which is doxo ubicin. This o en esul s in ca diac dys unc ion and myoca dial inju y
among o he s which can lead o long e m mo bidi y e en a e he discon inua ion o he d ug [1,2]. Doxo ubicin (DOX)-
induced ca dio oxici y has been sugges ed o esul s om ee adicals’ gene a ion and lipid pe oxida ion in myoca dial
cells [3,4]. These undesi able o gans oxici ies associa ed wi h doxo ubicin ha e limi ed i s clinical use ulness and
he e o e necessi a e ex ensi e esea ch in o agen s ha can p e en and o amelio a es hese oxic e ec s.
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
20
Tel ai ia occiden alis Hook is a lu ed pumpkin o he Cucu bi aceae amily widely consumed as ood in Nige ia [5]. I is
a popula ege able all o e Nige ia, especially in he Nige -Del a egion and he Eas e n pa o he coun y; a ie ies
o meals a e p epa ed om he lea es, s em and seeds o he plan [6]. The seeds a e e y nu i ious and a e ea en
oas ed o boiled. The seed has his o y o being e ec i e in he ea men and p e en ion o p os a e diso de s. The
seed ex ac has been epo ed o exe an idiabe ic [7], cellula an ioxidan , immunodula o y, an icance ,
an iin lamma o y [8], an iplasmodial [5], an ioxidan and analgesic [9,10], geno oxic and cy o oxic [11] and in i o
inhibi o y e ec alpha amylase and alpha glucosidase [12]. while he lea ex ac possesses an ioxidan , an ibac e ial
[13], hepa op o ec i e [14] an idiabe ic [15], an iplasmodial [5] geno oxic and cy o oxic [11] and an ip os a ic [16]
ac i i ies. Phy ochemical s udies o he seed ex ac ha e shown he p esence o alkaloid, la onoid, annins, e penes,
saponin, and ca diac glycosides [17]. Okokon e al. [8] epo ed he p esence o compounds such as pen adecanoic acid,
hexadecanoic acid; 16-oc adecenoic acid me hyl es e ; 9, 12-oc adecadienoyl chlo ide (Z,Z); 9- oc adecadienoic acid (Z)-
, 2, 3-dihyd oxyp opyl es e ; oc adecanoic acid; hexadecanoic acid,2,3-is[( ime hylsilyl) oxy] p opyl es e , 2,4-
hep adien-6-ynal,(E,E); benzoic acid ; dodecanoic acid ; linoleic acid e hyl es e ; hexadecanoic acid, me hyl es e ; α-
phelland ene; α-campholene aldehyde; e pinen-4-ol; ans-β-ocimene; bo neol and s igmas an-3- ol, in he seed
ex ac .
The p esen s udy was designed o e alua e he ac i i ies o seed ex ac and ac ions o T. occiden alis agains
doxo ubicin-induced ca dio oxici y in a s.
2. Ma e ials and Me hods
2.1. Plan collec ion and ex ac ion
F esh seeds o Tel ai ia occiden alis we e pu chased om I am ma ke in I u L. G. A, Akwa Ibom S a e, Nige ia, in June,
2023. The seeds we e p e iously iden i ied and au hen ica ed by a axonomis in he Depa men o Bo any, Uni e si y
o Uyo, Uyo, Nige ia. He ba ium specimens (UUPH 1(b)) we e deposi ed a Depa men o Pha macognosy and Na u al
Medicine He ba ium, Uni e si y o Uyo.
The esh seeds o he plan we e d ied on labo a o y able o 2 weeks and educed o powde . The seeds powde (1
kg) was mace a ed in 50% e hanol (5000 mL) o 72 hou s. The liquid il a es ob ained we e concen a ed a 40˚C and
all he e hanol was comple ely emo ed. The c ude ex ac (20 g) was dissol ed in 500 mL o dis illed wa e and
pa i ioned wi h equal olume o dichlo ome hane (DCM, 5 x 500 mL) ill no colou change was obse ed, o ob ain DCM
and aqueous ac ions. The ex ac and ac ions we e s o ed a 4˚C in a e ige a o un il used o he expe imen .
2.2. Animals
In his s udy, male albino Wis a a s (150-200 g) we e used. The animals we e sou ced om Uni e si y o Uyo Animal
house and shel e ed in plas ic cages. The a s we e ed wi h pelle ed s anda d Feed (Guinea eed) and gi en unlimi ed
access o wa e . The s udy was app o ed by College o Heal h Sciences Animal E hics Commi ee, Uni e si y o Uyo.
2.3. Expe imen al design
In his s udy, epea ed dose model ea lie desc ibed by Olo unda e e al. [18], which las ed o 14 days was used. G oups
I a s which se ed as he un ea ed con ol we e o ally p e ea ed wi h 10 mL/kg/day o dis illed wa e . G oup 2 a s
we e gi en no mal saline (10 mL/kg/day) bu equally ea ed in ape i oneally wi h 1.66 mg/kg o doxo ubicin
hyd ochlo ide dissol ed in 0.9% no mal saline on al e na e days o 14 days. G oups 3-5 a s we e o ally p e ea ed
espec i ely wi h 138 mg/kg/day, 276 mg/kg/day, and 553 mg/kg/day o Tel ai ia occiden alis seed ex ac dissol ed
in 10% Tween 80, 2 hou s be o e ea men wi h 1.66 mg/kg o doxo ubicin dissol ed in 0.9% no mal saline
adminis e ed in ape i oneally on al e na e days o 14 days. G oups 6 and 7 we e p e ea ed wi h 276 mg/kg o DCM
and aqueous ac ions espec i ely bu adminis e ed wi h 1.66 mg/kg o doxo ubicin dissol ed in 0.9% no mal saline
adminis e ed in ape i oneally on al e na e days o 14 days G oup 8 a s which se ed as he posi i e con ol g oup
we e equally p e ea ed wi h 100 mg/kg/day o silyma in wo hou s be o e ea men wi h 1.66 mg/kg o doxo ubicin
in 0.9% no mal saline adminis e ed in ape i oneally on al e na e days o 14 days.
2.4. Collec ion o blood samples and o gans
A e 14 days o ea men (24 hou s a e he las adminis a ion), he a s we e weighed again and sac i iced unde
ligh die hyl e he apou . Blood samples we e collec ed in o plain cen i uge ubes and allowed o s and o wo hou
be o e being cen i uged a 1500 pm o 15 mins o sepa a e he se um a oom empe a u e and used o biochemical
assays. The hea s o he a s we e su gically emo ed, weighed. Each hea was gen ly and ca e ully di ided in o wo
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
21
pa s; a pa was ixed in 10 % o maldehyde o his ological p ocesses, while he o he pa o he hea was b iskly
insed in ice cold 1.15% KCl solu ion and pu in a clean sample bo le. These we e s o ed in ice cold 0.9% NaCl.
2.5. Biochemical Assays
The s o ed se a samples collec ed om he a s used in his s udy we e used o he biochemical assays. The clea
samples we e ob ained o assays o he ollowing biochemical pa ame e s: se um ca diac oponin I, lac a e
dehyd ogenase (LDH), and c ea ine phosphokinase (CK-MB).
2.5.1. Measu emen o Ca diac ma ke Enzymes.
Ca diac enzymes (C ea ine phosphokinase –MB (CK-MB), lac ic acid dehyd ogenase (LDH), and oponin I we e
measu ed by using he ELISA ki . All he es s we e pe o med acco ding o he manu ac u e ’s ins uc ion. LDH (LDH
ki -Aspen Labo a o ies P . L d., Baddi; India.), T oponin I and CK-MB (Teco Diagnos ics, Anaheim, USA).
2.5.2. Assessmen o e ec o seed ex ac on lipid p o ile
The s o ed se a samples collec ed om he a s used in his s udy we e used o de e mine he lipid p o ile pa ame e s
such as se um choles e ol, iglyce ide and high-densi y lipop o ein (HDL) le els o he ea ed a s using s anda d
colo ime ic me hods [19]. These lipid pa ame e s de e mina ions we e done spec opho ome ically using Fo ess
Diagnos ic Ki s® acco ding o s anda d p ocedu es o manu ac u e ’s p o ocols. Low and e y low-densi y lipop o ein
(LDL and VLDL) we e es ima ed om he o mula o F iedwald e al. [20].
2.5.3. E ec o he seed ex ac on hea oxida i e s ess ma ke s
The pa s o hea samples s o ed in ice cold no mal saline we e used in p epa a ion o homogena es o assay o
oxida i e s ess ma ke s. Homogena es we e made in a a io o 1 g o we issue o 9 mL o 1.25% KCl by using mo o
d i en Te lon-pes le. The homogena es we e cen i uged a 7000 pm o 10 min a 4˚C and he supe na an s we e used
o he assays o supe oxide dismu ase (SOD) [21] , ca alase (CAT) [22], glu a hione pe oxidase (GPx) [23], educed
glu ha hione (GSH) [24] and malondialdehyde (MDA) con en [25]. These oxida i e s ess ma ke s we e used o assess
an ioxida i e s ess po en ials o he ex ac .
2.5.4. His opa hological s udies
The hea s’ pa s ixed in 10 % bu e ed o malin we e used o his ological p ocesses. They we e p ocessed and s ained
wi h haema o oxylin and eosin (H&E) [26], acco ding o s anda d p ocedu es a Depa men o Chemical Pa hology,
Uni e si y o Uyo Teaching Hospi al, Uyo. Mo phological changes we e obse ed and eco ded in he excised o gans o
he sac i iced animals. His ologic pic u es we e aken as mic og aphs.
2.6. S a is ical analysis
Da a collec ed we e analyzed using one way analysis o a iance (ANOVA) ollowed by Tukey K amme ’s mul iple
compa ison pos - es (G aph pad p ism so wa e Inc. La Jolla, CA, USA). Values we e exp essed as mean ± SEM and
signi icance ela i e o con ol we e conside ed a p˂0.001 and p˂0.05.
3. Resul s
3.1. E ec o seed ex ac and ac ions o T. occiden alis on body and o gans weigh s o a s wi h doxo ubicin-
induced oxici y
Adminis a ion o T. occiden alis seed ex ac and ac ions o a s wi h doxo ubicin-induced o gans oxici ies caused
conside able imp o emen o he body weigh s compa ed o he o gano oxic g oup. The c ude ex ac (276 mg/kg) and
dichlo ome hane ac ion ea ed g oups eco ded he highes body weigh gains compa ed o he o gano oxic g oup.
Howe e , hese we e non-dose-dependen and insigni ican when compa ed o he o gano oxic g oup. The hea
weigh s o he g oup ea ed wi h doxo ubicin only we e ound o be inc eased when compa ed o hose o he no mal
con ol g oup hough no s a is ically signi ican (p>0.05). Howe e , concommi an ea men o a s wi h doxo ubicin
and seed ex ac and ac ions o T. occiden alis imp o ed he o gans weigh s hough insigni ican ly (p>0.05) ela i e o
he g oup ea ed wi h doxo ubicin only (Table 1).
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
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3.2. E alua ion o e ec o seed ex ac and ac ions o T. occiden alis on ca diac ma ke enzymes o
doxo ubicin-induced hea inju ies in a s:
The e ec o seed ex ac and ac ions o T.occiden alis on ca diac ma ke enzymes o no mal a s and a s wi h
doxo ubicin-induced oxici ies is as p esen ed in Table. T ea men o a s wi h doxo ubicin (1.66 mg/kg i.p) on al e na e
days o 14 days caused signi ican (p<0.01-0.001) ele a ion o ca diac ma ke enzymes ( oponin I, lac a e
dehyd ogenase and CK-MB) ac i i ies when compa ed o no mal con ol. The inc eases in he le els o lac a e
dehyd ogenase, oponin I and CK-MB we e dose-dependen ly and signi ican ly (p< 0.05-0.001) educed when
compa ed o o gano oxic g oup ollowing concomi an ea men o he a s wi h seed ex ac and ac ions o
T.occiden alis (138-553 mg/kg) wi h he highes dose o he ex ac (553 mg/kg) and aqueous ac ion ha ing he
highes e ec . Simila e ec was obse ed in he g oup ea ed wi h silyma in. (Figu es 1, 2 and 3).
3.3. E ec o T. occiden alis seed ex ac and ac ion on hea oxida i e s ess ma ke s o doxo ubicin-induced
hea oxici y
Table 2 shows he e ec o T. occiden alis seed ex ac / ac ions on oxida i e s ess ma ke s o he hea . Adminis a ion
o doxo ubicin (1.66 mg/kg i.p) on al e na e days o 14 days caused dec eases o ca diac an ioxidan enzymes ac i i ies
(SOD, GPx, GST, CAT) and GSH le els which we e signi ican (p<0.05-0.001) when compa ed o con ol excep in CAT
le el. The MDA le el was also signi ican ly (p<0.01) ele a ed by doxo ubicin ea men ela i e o con ol. Howe e ,
concomi an adminis a ion o seed ex ac / ac ions o T.occiden alis (138- 553 mg/kg) wi h doxo ubicin o 14 days
caused ma ked ele a ions o he enzyma ic and non-enzyma ic endogenous an ioxidan s in he ea ed a s’ g oups
when compa ed o he o gano oxic g oups. The ele a ions in he le els o SOD and CAT we e dose-dependen and
signi ican (0.05-0.01) in he g oups ea ed wi h he highes dose (553 mg/kg). DCM ac ion ea ed g oup had he
mos signi ican (p<0.001) ele a ion o SOD, while CAT le el was signi ican ly (p<0.001) aised by aqueous ac ion
when compa ed o con ol. GPx and GSH le els we e also dose-dependen ly ele a ed wi h DCM ac ion ea ed g oup
ha ing he mos signi ican (p<0.001) e ec when compa ed o o gano oxic g oup. The ea men wi h ex ac / ac ions
also caused ma ked non-dose-dependen educ ion in he le el o MDA o he ea ed a s which we e signi ican
(p<0.05-0.001) in he g oups ea ed wi h he low dose (138 mg/kg), aqueous ac ion, DCM ac ion and silyma in
when compa ed o o gano oxic con ol wi h he DCM ac ion ha ing he mos signi ican e ec (Table 2).
3.4. E ec o seed ex ac and ac ion o T.occiden alis on lipid p o ile o a s wi h doxo ubicin -induced o gans
oxici ies
Adminis a ion o doxo ubicin (1.66 mg/kg) was obse ed o caused signi ican (p<0.05-0.001) ele a ion in le els o
o al choles e ol, iglyce ide, high densi y lipop o ein, low densi y lipop o ein, and e y low-densi y lipop o ein. These
aised le els o o al choles e ol, iglyce ide, high densi y lipop o ein, low densi y lipop o ein, and e y low-densi y
lipop o ein we e signi ican ly (p<0.05-0.001) educed when compa ed o o gano oxic g oup ollowing concommi an
ea men wi h seed ex ac and ac ions o T.occiden alis and silyma in. Howe e , he educ ions in o al choles e ol
and low-densi y lipop o ein we e dose-dependen , while non-dose-dependen educ ions we e obse ed in
iglyce ide, high densi y lipop o ein and e y low-densi y lipop o ein le els (Table 3).
3.4.1. E ec o seed ex ac and ac ions o T. occiden alis on his ology o a hea in doxo ubicin-induced ca dio oxici y:
His ologic sec ions o hea s o a s ecei ing a ious ea men s a magni ica ion (x100) s ained wi h H&E me hod
e ealed ha G oup 1 (no mal con ol, CONT) ea ed dis illed wa e (10 mL/kg) had ca diac sec ion showing no mal
ca diac a chi ec u e wi h he myome ium ha ing well-p esen ed ca diac myocy es, myocy e nuclei, ib ocy e nuclei
and endomysium and blood essels. No pa hological change was seen. The o gano oxic g oup (G oup 2, T+CONT)
ea ed wi h doxo ubicin (1.66 mg/kg) only e ealed hea issue showing p esence o in e -muscula ascula
hemo hage and ib osis wi hin he ca diac myome iume. Focal hyaline degene a ion was also seen. G oup 3 (T+STD)
ea ed wi h 100 mg/kg o silyma in o T.occiden alis seed and doxo ubicin (1.66 mg/kg) had mode a ely a ec ed hea
issue showing p esence o in e -muscula ascula hemo hage wi hin he ca diac myome ium. Ra s in g oup 4
(T+LDE) ea ed wi h 138 mg/kg o T.occiden alis seed ex ac and doxo ubicin (1.66 mg/kg) showed mode a ely
a ec ed ca diac issue e ealing he p esence o ib osis wi hin he ca diac myome ium. G oup 5 (T+MDE) ea ed
wi h 276 mg/kg o T. occiden alis seed ex ac and doxo ubicin (1.66 mg/kg) showed hea issue showing p esence o
in e -muscula ascula hemo hage and ib osis wi hin he ca diac myome ium. G oup 6 (T+HDE) ea ed wi h 553
mg/kg o T. occiden alis seed ex ac ex ac and doxo ubicin (1.66 mg/kg) showed mode a ely a ec ed hea issue
showing he p esence o in e -muscula ascula hemo hage and ib osis wi hin he ca diac myome ium. G oup 7
(T+AQE) ea ed wi h 276 mg/kg o aqueous ac ion o T. occiden alis seed and doxo ubicin (1.66 mg/kg) showed a
mode a ely a ec ed hea issue showing he p esence o ib osis wi hin he ca diac myome ium. Ra s in g oup 8
(T+DCME) ea ed wi h 276 mg/kg o dichlo ome hane ac ion o T. occiden alis seed and doxo ubicin (1.66 mg/kg)
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
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mode a ely a ec ed hea issue showing he p esence o in e -muscula ascula hemo hage and ib osis wi hin he
ca diac myome ium (Figu e 4).
Table 1 E ec o T. occiden alis seed ex ac on body and o gans weigh s o a s wi h doxo ubicin-induced oxici y
Pa ame e s/
T ea men
Dose
mg/kg
Hea
Body weigh
Be o e
A e
% inc ease in body weigh
No mal con ol
-
0.60± 0.06
176.28±17.97
198.25± 6.61
12.46
Doxo ubicin
1.66
0.65± 0.01
169.66 ± 6.80
181.66±13.24
5.72
Silyma in+DOX
100
0.63±0.03
180.33± 10.86
190.66± 13.24
5.72
Ex ac +DOX
138
0.65±0.05
176.0± 11.13
191.0± 6.08
8.52
276
0.58±0.06
167.0± 7.57
185.0 ± 8.73
10.77
553
0.65±0.03
177.66± 7.42
193.33 ± 5.48
8.82
Aqueous ac ion
276
0.69±0.10
187.66± 17.89
195.33± 17.70
4.08
DCM ac ion
276
0.52±0.06
162.66± 12.66
180.33± 9.56
10.86
Da a a e exp essed as mean ±SEM. signi ican a dp<0.001 when compa ed o no mal con ol; ap< 0.05, bp< 0.01, cp< 0.001 when compa ed o
o gano oxic con ol. n = 5.
Da a a e exp essed as MEAN ± SEM, Signi ican a bp<0.01; cp<0.001 when compa ed o no mal con ol; dp<0.05 when compa ed o o gan oxic
con ol; *p< 0.001 (n=5).
Figu e 1 E ec o T.occiden alis seed ex ac and ac ions on C ea ine phosphokinase-MB enzyme o a s wi h
doxo ubicin-induced hea oxici y
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
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Da a a e exp essed as MEAN ± SEM, Signi ican a cp<0.001 when compa ed o no mal con ol; p< 0.001, when compa ed o o gano oxic con ol
(n=5).
Figu e 2 E ec o T. occiden alis seed ex ac and ac ions on T oponin I enzyme o a s wi h doxo ubicin-induced
hea oxici y
Da a a e exp essed as MEAN ± SEM, Signi ican a cp<0.001 when compa ed o no mal con ol; p< 0.001, when compa ed o o gano oxic con ol
(n=5).
Figu e 3 E ec o T.occiden alis seed ex ac and ac ions on lac a e dehyd ogenase enzyme o a s wi h
doxo ubicin-induced hea oxici y
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
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Table 2 E ec o T. occiden alis seed ex ac and ac ions on ca diac oxida i e s ess ma ke s o a s wi h doxo ubicin-
induced oxici y
T ea men
Dose
mg/kg
SOD
(U/ml)
CAT
(U/g o p o ein)
GPX
(µg/ml)
GSH
(µg/ml)
MDA
(µMol/ml)
Con ol
10
0.29± 0.01
1.86±0.02
0.056±0.003
2.57± 0.01
0.45± 0.01
Doxo ubicin
1.66
0.18± 0.02a
1.42±0.08
0.050±0.005a
2.23± 0.01b
0.64± 0.02b
C ude ex ac
138
0.20±0.03
2.32±0.38
0.050±0.003a
2.49± 0.14
0.47±0.01e
276
0.22±0.03
2.61±0.17
0.056±0.002d
2.50± 0.13
0.54±0.05
553
0.28±0.02d
3.42± 0.16a,
0.056±0.002d
2.53± 0.12
0.58±0.02
Aqueous F ac ion
276
0.28±0.03d
3.01±0.61e
0.049±0.005b
2.17± 0.01a
0.48± 0.04d
DCM ac ion
276
0.35±0.02
2.36±0.16
0.067±0.008c,
3.06± 0.04b,
0.41± 0.05
Silyma in
100
0.28±0.02d
1.63±0.27
0.045±0.008c
2.38± 0.03a
0.47±0.01e
Da a a e exp essed as MEAN ± SEM, Signi ican a ap<0.05, bp<0.01, cp<0.001, when compa ed o con ol; Signi ican a dp<0.05, ep<0.01, p<0.001
compa ed o o gano oxic g oup. (n=5)
Table 3 E ec o T. occiden alis seed ex ac and ac ions on lipid p o ile pa ame e s o a s wi h doxo ubicin-induced
oxici y
T ea men
Dose
mg/kg
To al choles e ol
(MMOL/L)
T iglyce ide
(MMOL/L)
HDL-C
(MMOL/L)
LDL-C
(MMOL/L)
VLDL
(MMOL/L)
Con ol
10
3.33± 0.20
1.21±0.03
1.30±0.02
2.70± 0.22
0.56± 0.02
Doxo ubicin
1.66
4.60± 0.15b
1.55±0.05c
1.60±0.06a
3.70± 0.09c
0.70± 0.02
C ude ex ac
138
3.80±0.11
1.31± 0.03e
1.44±0.01
2.95± 0.11e
0.60±0.01
276
3.33±0.23
1.35±0.03d
1.45±0.04
2.49± 0.20
0.61±0.01
553
2.63±0.17
1.14±0.02
1.23±0.04e
1.92± 0.13
0.51±0.01e
Aqueous
F ac ion
276
2.53±0.17
1.08±0.07
1.23±0.06e
1.78± 0.15a,
0.49± 0.03e
DCM ac ion
276
2.40±0.17
1.08±0.02
1.19±0.07e
1.70± 0.14a,
0.49± 0.04e
Silyma in
100
3.00±0.28
1.09±0.06
1.20±0.07e
2.29± 0.24
0.48± 0.04e
Da a a e exp essed as MEAN ± SEM, Signi ican a ap<0.05, bp<0.01, cp<0.001, when compa ed o con ol; Signi ican a dp<0.05, ep<0.01, p<0.001
compa ed o o gano oxic g oup. (n=5)
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
26
Figu e 4 Pho omic og aphs o sec ions o hea s o a s ea ed wi h dis illed wa e (CONT), doxo ubicin only,1.66
mg/kg (T.CONT), Sylima in,100 mg/kg and DOX(T+STD), T occiden alis, 138 mg/kg and DOX (T+LDE),T.occiden alis,
276 mg/kg and DOX (T+MDE), T.occiden alis, 553 mg/kg and DOX (T+HDE), Aqueous ac ion,276 mg/kg and DOX
(T+AQE) and DCM ac ion, 276 mg/kg and DOX (T+DCME) showing well-p esen ed ca diac myocy es (Cm), myocy e
nuclei (Mn), ib ocy e nuclei (Fn) and endomysium (En) and blood essels (B ),in e -muscula ascula hemo hage
( ed a ow) and ib osis (black a ow) (H&E x 100)
4. Discussion
Doxo ubicin (DOX) is an an h acycline glycoside an ibio ic wi h po en an icance ac i i y [27], whose clinical
use ulness has been ma ed by i e e sible and dose-dependen ca diomyopa hy, neph o oxici y and hepa o oxici y
induced by he d ug despi e ha ing a high he apeu ic index [2]. DOX al e s s uc u al and unc ional p ocesses due o
i s high a ini y o phospholipids in he mi ochond ial memb ane in he ca diac cells [1] , hus esul ing in nucleic acid
damage, sa come e dis up ion, and myo ib il loss [28]. These undesi able e ec s ha e been aced o he ac i i ies o
i s me aboli e, DOX-semiquinone, which eac s wi h O2, p oducing H2O2 and O2− (supe oxide) [3], and inhibi s he
GSC Biological and Pha maceu ical Sciences, 2025, 33(01), 019-030
27
ac i i ies o endogenous enzyma ic and nonenzyma ic an ioxidan s he eby c ea ing oxida i e s ess wi h damaging
e ec on he hea compa ed wi h o he o gans such as he kidney and li e [3,4].
This s udy was designed o assess he an i oxican po en ials o seed ex ac and ac ions o Tel ai ia occiden alis
agains DOX-induced ca dio oxici y. The in ape i oneal adminis a ion o DOX showed ca diomyopa hy mani es ed by
aised le els o CK-MB, oponin I, and LDH and a e consis en wi h ea lie s udies [29]. I has been obse ed ha he
mo ali y a e in animals ea ed wi h DOX was 40% compa ed wi h he no mal con ol g oup be o e he end o
expe imen which may be due o accumula ion o asci es esul ing om abno mali y in ca diac unc ioning [30]. Asci es
is hough o de eloped due o ex acellula olume expansion and luid leakage owa ds in e s i ium due o ubula
diso de and sodium e en ion as p oposed in p e ious s udies [31]. Co-adminis a ion o he seed ex ac o T.
occiden alis in his s udy was obse ed o educe he le els o oponin I, LDH and CK-MB, po aying a signi ican
ca diop o ec i e ac i i y. This ac i i y can be a ibu able o he ee adicals sca enging ac i i ies o he phy ochemical
cons i uen s o he seed ex ac as epo ed p e iously [8,9,13].
Reac i e oxygen species gene a ion, in lamma o y p ocesses and lipid pe oxida ion ha e been sugges ed o be
esponsible o doxo ubicin-induced ca dio and hepa o oxici y [32,33].
The indings o his s udy show ha adminis a ion o doxo ubicin (1.66 mg/kg, i.p) on al e na e days o 14 days o
a s caused signi ican dec eases (p<0.05) in le els o enzyma ic and non-enzyma ic endogenous an ioxidan s (SOD,
CAT, GPx and GSH) in he hea and ele a ed le el o MDA when compa ed o con ol. Lipid pe oxida ion is a ma ke o
oxida i e s ess and ele a ions in he amoun o malondialdehyde (MDA), a lipid pe oxida ion p oduc , ha e been
epo ed ollowing Dox ea men [34,35,36]. Simila end was obse ed in his s udy. Coadminis a ion o seed ex ac
and ac ions o T. occiden alis (138 - 553 mg/kg) wi h doxo ubicin caused signi ican (p<0.05-0.001) non-dose-
dependen ele a ion in he le els o he an ioxidan enzymes (SOD, CAT, GPx) when compa ed o con ol. Simila ly, GSH
le el was signi ican ly (p<0.001) ele a ed ollowing ea men wi h he ex ac when compa ed o con ol. Simila ly,
he e we e signi ican (p<0.05-0.01) educ ions in he le el o MDA o he ex ac - ea ed a s. I has been documen ed
ha DOX inhibi s he ac i i ies o endogenous enzyma ic and nonenzyma ic an ioxidan s as was he case in his s udy.
So, an imbalance be ween ROS gene a ion and neu aliza ion leads o oxida i e s ess and inju y o he hea [3,4,28].
The seed ex ac po en ials o educe he le el o MDA shows a educ ion in lipid pe oxida ion and gene a ion o ee
adicals which migh ha e been sca enged by he phy ocons i uen s p esen in his ex ac , hence he p o ec i e e ec
on he hea .
His ological sec ions o a hea s ea ed wi h doxo ubicin alone showed sec ion wi h degene a ing ca diac muscle
ibe s which is a mani es a ion o he e ec o doxo ubicin oxici y due o he e ec o ee adicals gene a ed by he
d ug. Howe e , co-adminis a ion o T. occiden alis seed ex ac / ac ions and doxo ubicin educed he e ec o
doxo ubicin as was seen in mild e ec o absen o pa hological signs con i ming he ca diop o ec i e e ec o Tel ai ia
occiden alis seed. This e ec can be a ibu ed o he an ioxidan ac i i ies o he phy ochemical cons i uen s o he seed
ex ac such as he mono e penes and polyunsa u a ed a y acid (PUFA) p e iously epo ed in his seed ex ac which
ha e been documen ed o exe an ioxidan ac i i ies [8].
Howe e , doxo ubicin was ound o aised signi ican ly he le els o o al choles e ol, iglyce ide, HDL, LDL and VLDL.
This esul is consis en wi h ha o Okokon e al. [37]. Howe e , his po ays a se ious isk o he hea and also
indica es lipolysis p omo ion ac i i y o he d ug which leads o inc ease in he lipid p o ile pa ame e s. Inc eases in
lipid p o ile pa ame e s ha e been linked o hea diseases [38]. The educ ion o he aised le els o o al choles e ol,
iglyce ides, VLDL, LDL and HDL in his s udy e eals a s ong hypolipidemic ac i i y o he seed ex ac and ac ions
pe haps due o inhibi o y ac i i y on lipolysis which is due o he ac i i ies o i s phy ocons i uen s. This u he
con i ms he ca diop o ec i e po en ials o he seed ex ac and ac ions
This e ec can be a ibu ed o he an ioxidan ac i i ies o he phy ochemical cons i uen s o he seed ex ac
p e iously epo ed in his seed ex ac which ha e been documen ed o exe an ioxidan ac i i ies [8].
5. Conclusion
The indings o his s udy show ha he seed ex ac and ac ions o Tel ai ia occiden alis ha e he po en ials o
coun e ac he inju ious e ec o doxo ubicin on he hea . This ac i i y can be a ibu ed o he an ioxidan and
an ioxida i e s ess ac i i ies o i s phy ochemical cons i uen s. Thus, he seed can be use o alle ia e and/o p e en
doxo ubicin-induced ca dio oxici y.
